Interstitial Cystitis prostatitis

							                         排尿障礙治療中心 版權所有




Interstitial Cystitis
Painful Bladder Syndrome


            Hann-Chorng Kuo
          Department of Urology
 Buddhist Tzu Chi General Hospital Hualien
                            排尿障礙治療中心 版權所有



Interstitial cystitis
   A syndrome of mystery in urology
   A diagnosis of exclusion
   Triad diagnostic characteristics –
    Suprapubic pain at full bladder and
    relieved after voiding, with severe
    frequency and nocturia
    Sterile urine
    Characteristic cystoscopic findings
                             排尿障礙治療中心 版權所有



Diseases associated with IC
  Allergies, autoimmune diseases, rheumatic
   disease,irritable bowel syndrome
  A common pathophysiology mediated by
   immune, endocrine & neurologic dysfunction
  Systemic lupus erythematosus
  The role of mast cell (increase histamine
   release from bladder biopsies) in IC
                            排尿障礙治療中心 版權所有



Epidemiology of IC
  In a survey of USA Nurse’s health
   Study, self-reported IC was 0.4% (357
   in 91155 NHSI) and 1.4% (1354 in
   993428 NHSII)
  NIDDK criteria is too restrictive, about
   60% excluded patients may have IC
  The prevalence of IC was estimated to
   be 52 per 105 (NHSI) and 67 per 105
                              排尿障礙治療中心 版權所有



Possible pathogenesis of IC
  Post-infection autoimmune process
  Mast cell activation – inflammation, toxin,
   stress
  Urothelial dysfunction – increased
   permeability of urothelium
  Neurogenic inflammation – K diffusion- mast
   cell activation – upregulation of sensory
   fiber – release of neuropeptide (substance
   P) – neurogenic inflammation – pain in IC
                           排尿障礙治療中心 版權所有

Characteristic cystoscopic
findings after hydrodilatation
  Classical IC – contracted bladder,
   Hunner ulcer
  Early IC – glomerulation, petechial
   hemorrhage, mucosal fissure
  Recent investigations revealed classical
   IC may be misleading, chronic IC may
   be more accurate to describe pathology
                                      排尿障礙治療中心 版權所有



Interstitial cystitis
     1915 Hunner – an elusive ulcer after secondary
      bladder hydrodilation
     1949 Hand – Female tomale ratio 11:1
     1975 Oravisto – incidence about 18/105
     1978 Messing – Glomerulation after hydrodilatation
     1982 Larsen – mast cell quantitative assessment in IC
     1983 Parsons – a defect in bladder GAG layer
     1987 Holm-Bentzen – painful bladder syndrome
     IC remains a syndrome of unknown etiology, difficult
      to diagnosis and treatment
                                  排尿障礙治療中心 版權所有
IC patient accrual form –NIDDK
1987 automatic exclusion
    Less than 18 years old
    Benign or malignant bladder tumor
    Irradiation cystitis
    Tuberculous cystitis
    Bacterial cystitis
    Vaginitis
    Cyclophosphamide cystitis
    Symptomatic urethral diverticulum
    Uterine, cervical, vaginal, or urethral cancer
                                 排尿障礙治療中心 版權所有

IC patient accrual form
-- automatic exclusion
    Active herpes
    Bladder or lower ureteral calculi
    Waking frequency < 5/12 hours
    Nocturia <2/night
    Symptoms relieved by antibiotics, urinary
     antiseptics, analgesics
    Involuntary detrusor contractions
    Capacity > 400ml, no sensory urgency
                                 排尿障礙治療中心 版權所有

IC patient accrual form
-- automatic inclusions
    Hunner’s ulcer
    Positive factors –
    Pain on bladder filling relieved by emptying
    Pain (suprapubic, pelvic, urethral, vaginal,
     perineal)
    Glomerulation on endoscopy
    Decreased compliance on cystometry
    Bladder distention by 80 cm water x 1 min,
     two positive factors are necessary
                                    排尿障礙治療中心 版權所有



Cystoscopic Hydrodilatation
  Intravenous general anesthesia or spinal anesthesia
  Inserting cystoscopy lightly, do not evacuate bladder
   completely
  Inspection the whole bladder for vasculature and
   lesions
  The fluid level is set at 80 cm water above symphysis
   pubis
  Fully distended the bladder
  Evacuation of the bladder slowly and observe any
   glomerulation, petechial, splotch hemorrhage or
   mucosal laceration
  Refilled the bladder and check ulceration
  Take bladder biopsy if necessary
                    排尿障礙治療中心 版權所有



Glomerulation and petechia
                    排尿障礙治療中心 版權所有

Increased vasculature in
a man with IC
                             排尿障礙治療中心 版權所有



Interstitial cystitis in Men
   Less than 10% of IC are men
   35/60 (58%) men with non-bacterial
    prostatitis or prostatodynia had
    petechiae following cystoscopic dilation
   In 29 men with IC, misdiagnosis
    wasmade as prostatitis (48%), BPH
    (38%)
   Carcinoma in situ should be ruled out
                            排尿障礙治療中心 版權所有

Management after cystoscopic
Hydrodilatation for IC
  Indwelling a Foley catheter especially
   after bladder biopsy
  Adequate hydration
  Hemorrhage is usually not a problem
  Analgesics for severe irritative
   symptoms
  Remove the catheter after fully
   awakened
                           排尿障礙治療中心 版權所有



Basic urodynamic abnormalities
  Sensory urgency
  Intolerance to increments of bladder
   volume
  Decrease in bladder compliance
   <30ml/cm water (16/30 v 3/17 PBS,
   p<0.025)
  Smaller maximal capacity under
   anesthesia (548 v 612, p<0.05)
                           排尿障礙治療中心 版權所有



Urodynamic findings in IC
  50 patients with painful bladder
   underwent urdynamic study and
   cystoscopic hydrodilation
  30 (28 F & 2 M) had characteristic IC,
   20 non-IC
  Symptomatology was indifferent
   between IC & non-IC
                                       排尿障礙治療中心 版權所有



Symptomatology of 30 IC
                                     IC(N=30) Non-IC(n=20)
Frequency                              30          20
Urgency                                14          7
Nocturia(>two/night)                   30          20
Small urine amount                     28          17
Dysuria                                25          13
Suprapubic pain on bladder filling     28          14
Pain relieved after voiding            25          13
Lower abdominal discomfort              2          6
Gross hematuria                         2          -
Other somatic complaints                3          11
Duration of symptoms > two years       29          20
Treated as cystitis                    25          13
                                             排尿障礙治療中心 版權所有



Uroflowmetry in IC patients
                                     IC (n=28)   Non-IC (n=16)   Statistics*

Voided volume             ≦ 350         20            9
     (mL)                 >350          8             7           P>0.1
                          mean       277±101       319±124        P >0.1

Maximal flow rate         ≦ 20          16            10
   (mL/sec)
                          >20           12            6           P >0.1
                          mean       18.8±6.9      20.7±8.2       P >0.2
Corrected max.flow rate   mean       1.15±0.42     1.19±0.38      P >0.3
Flow pattern              normal        6             5
                          abnormal      22            11          P >0.1
                   排尿障礙治療中心 版權所有

Various Types of Abnormal
Uroflowmetry in IC (1)
                   排尿障礙治療中心 版權所有

Various Types of Abnormal
Uroflowmetry in IC (2)
                   排尿障礙治療中心 版權所有

Various Types of Abnormal
Uroflowmetry in IC (3)
                          排尿障礙治療中心 版權所有



Uroflowmetry in IC
  Most IC patients present with abnormal
   flow pattern
  With or without a low maximal flow rate
   (22/28), but this feature also can be
   found in non-IC (11/16)
  Can rule out other hypersensitive
   bladder and bladder outlet obstruction
                                                  排尿障礙治療中心 版權所有



Urodynamic results in IC
                                     IC (n=30)     Non-IC (n=17)   Statistics*

First sensation of filling   ≦ 100   20            9
 (mL)                        >100    10            8               P>0.1
                             mean    100.9±38      112.4±45.7      P >0.1
Tolerable capacity
                             ≦ 400   25            15
  (mL)
                             >400    5             2               P >0.1
                             mean    307.4±89.2    303.1±79.7      P >0.4
Compliance                   ≦ 30    16            3
  (mL/cmH2O)                 >30     14            14              P <0.025
                                  排尿障礙治療中心 版權所有



Urodynamic parameters in IC
    Bladder hypersensitivity FSF <100ml
    A trend toward smaller capacity in chronic
     cases
    Most have normal compliance in early IC and
     decreased compliance in classic IC
    Most have a normal flow rate
    Urethral pressure profile has no clinical value
    As prognostic indicators and surgical results
                  排尿障礙治療中心 版權所有

Normal and abnormal
cystometry in IC
                    排尿障礙治療中心 版權所有



Abnormal cystometry in IC (1)
                    排尿障礙治療中心 版權所有



Abnormal cystometry in IC (2)
                    排尿障礙治療中心 版權所有



Abnormal cystometry in IC (3)
                               排尿障礙治療中心 版權所有



Pathological findings in IC
pathology                      IC (n=24)
                      Absent    Mild       Marked
Mucosal erosion         2        12         10
Submucosal edema        3        19          2
Vascular dilation       6        13          5
NMC infiltration        2        21          1
Intravascular PMN       9        10          5
Plasma cell            21        2           1
Granulation tissue
Endothelial cell       23        -           1
Fibroblast
 proliferation         22        1           1
Squamous metaplasia    23        -           1
Mast cell count         -        19          5
                      排尿障礙治療中心 版權所有



Microscopic finding in early IC
                     排尿障礙治療中心 版權所有

Microscopic findings in
Chronic IC
                              排尿障礙治療中心 版權所有



Microscopic findings in IC
  Classical IC – mucosal ulceration with
   granulation tissue; marked mononuclear cell
   infiltration; increased mast cell in lamina
   propria and detrusor; presence of
   intraurothelial mast cell; perineural
   inflammatory cell; significant fibrosis
  Early IC – mucosal rupture; suburothelial
   hemorrhage; scanty inflammation and mild
   submucosal edema
                    排尿障礙治療中心 版權所有



Detrusor Mastocytosis in IC
                           排尿障礙治療中心 版權所有



Physiology of Micturition
  Bladder sensation: first sensation
   150ml, full sensation 250-350ml, urge
   sensation 400-500ml
  Sensory afferents – reflex center S2-4 –
   micturition center (pons) – cerebral
   cortex
  Voiding pressure in women 20-40 cm
   water, men 30-50 cm water
                     排尿障礙治療中心 版權所有

Bladder mucosa and
vasculature
                           排尿障礙治療中心 版權所有



Vesical Blood Urine barrier
  Urothelium appears to be a functional
   extension of renal collecting duct
  Absence of barrier allows recirculation
   of renal waste and deteriorate function
  13:1 mucosal to muscular blood flow in
   bladder wall ratio imply a barrier
   function for blood-urine compound
   exchange and equilibrium
                           排尿障礙治療中心 版權所有

Increased bladder mucosal
permeability
  Acute bacterial cystitis
  Chronic cystitis
  Foreign body, calculi, tumor
  Overdistension
  Acidic fluid or toxin substance
  Surgical trauma or instrumentation
                             排尿障礙治療中心 版權所有

Increased permeability of
Bladder epithelium
  Bladder capacity was decreased by K,
   hyperosmolar, and PH5; while increased by
   hypoosmolarity electrolyte free media,
   furosemide, and PH8
  Normal subjects absorbed 4.3%, IC 25% of
   concentrated urea from bladder
  Frequent voiding reduced urinary contact
   time, protecting from urine recirculation
                              排尿障礙治療中心 版權所有

Pathophysiology of Leaky
epithelium and cystometry
  Impairment of blood urine barrier led to a
   decrease in compliance and capacity
  Isotonic KCl and hyperosmolar NaCl induced
   an immediate onset of voiding contraction in
   rat bladders
  CMG in normal bladder revealed no such
   effects of KCl & hyperosmolar NaCl
  Urge sensation and pressure are elicited in
   diseased human bladder after intravesical K
                               排尿障礙治療中心 版權所有



Potassium and Bladder control
  Bladder sensory afferent pathway relative to
   submucosal K and intramuscular
   proprioceptor to to intravesical pressure and
   tension
  Intravesical K or hyperosmolarity affects
   exteroception resulting in reflective storage
   pressure elevation and urge proprioception
  Local or perimuscular K enhancement
   facilitates onset of voiding contraction
                               排尿障礙治療中心 版權所有

Glycosaminoglycan &
Frequency urgency syndrome
  A subset of frequency urgency syndrome has
   a leaky epithelium and cations (K) can diffuse
   subepithelially and provoke urgency
   frequency
  Intravesical KCl (0.4M) provoked symptoms in
   4.5% normal, 70%IC, 18% heparin treated
   IC, 100% irradiation cystitis
  Intravesical sulfated polysaccharide can
   restore injured urothelium to normal
                               排尿障礙治療中心 版權所有

Pathophysiology of
Leaky Epithelium
  Hyperosmolar NaCl concentration decreased
   more rapidly in over-distension, retention,
   bacterial and chronic cystitis
  Serious water inflow and recirculation of renal
   waste occurred in urine retention
  In experimental cystitis, slow blood flow rate
   resulted in maximal hyperosmolar
   suburothelial urea accumulation (maximal
   exchange)
                                 排尿障礙治療中心 版權所有



Treatment of Interstitial Cystitis
     Cystoscopic hydrodilatation
     Intravesical heparin therapy
     Intravesical DMSO instillation
     Intravesical capsaicin or resiniferatoxin
     Sodium pentosan polysulfate (PPS, Elmiron)
     Amitriptynin
     Supratrigonal cystectomy augmentation
                                排尿障礙治療中心 版權所有



Medical treatment of IC
    Cyclosporine
    Methotrexate
    Tice strain BCG– 60% response rate vs 27%
     in placebo
    Elmiron (PPS 100mg tid) – 6.2% to 18.7%
     response rate
    Electromotive administration of intravesical
     lidocaine & dexamethasone – 62% effective
                          排尿障礙治療中心 版權所有



Inravesical Heparin therapy
  Patients with urgency frequency and a
   positive potassium test
  Intravesical Heparin 25000u/10ml saline
   and holding for 2 hours
  2x or 3x per week for 12 weeks
  67% patients have improvement in
   symptoms and increase in bladder
   capacity
                      排尿障礙治療中心 版權所有

Urodynamic finding before and
after Heparin Therapy
                                        排尿障礙治療中心 版權所有

The changes of urodynamic parameters
before and after heparin treatment
                            Baseline    3 months     Statistics
                                                      P value
  FSF(ml)                  96.5±46.4    146.1±55.4     0.001
  US(ml)                   225.4±96.2   264.9±84.2     0.009
  Cystometric capacity(ml) 262.0±89.8   304.3±84.8     0.002
  PdetQmax(cmH2O)           25.7±9.1     28.3±9.3      0.07
  Qmax (ml/sec)             12.9±5.7     15.1±7.7      0.063
  Residual urine(ml)       29.4±38.4    14.5±25.7      0.096
  IPSS (points)             19.5±4.6     9.0±4.0         0
  Nocturia (times/night)    5.7±2.0      2.3±1.1         0
  Pain scale of KCl         3.2±0.5      0.7±0.7         0
  (points)
                            排尿障礙治療中心 版權所有



Intravesical Capsaicin Therapy
  Capsaicin in 10 uM concentration
   instilled intravesically 1/week to 10
   women with hypersensitive
   bladder(HSB) and 10 with interstitial
   cystitis, a total 6 weeks
  8 HSB responded for 3-5 days, 2 IC
   responded for 2-3 days
  No reported side effects
                           排尿障礙治療中心 版權所有



Cystoscopic hydrodilatation
  Under general or spinal anesthesia, at
   pressure of 80cm water, the bladder
   was distended for 30min
  Effective in relieving symptoms after
   hydrodilatation
  The increased bladder capacity was
   limited
  Regular hydrodilatation is needed
                           排尿障礙治療中心 版權所有



Cystectomy & augmentation
  Supratrigonalor subtrigonal cystectomy
   plus enterocystoplasty are effective
  Major operation with complication
  Residual LUTS including pain persist in
   30% of patients
  Only suitable in severe classical IC
                            排尿障礙治療中心 版權所有



Bladder autoaugmentaton
  A minor operation to relieve intravesical
   pressure
  Myomectomy or detrusectomy and open
   bladder wall
  Increased bladder capacity and pain at
   full bladder can be relieved
  Covering of omentum or de-epithelial
   bowel musculature will be helpful
                  排尿障礙治療中心 版權所有



Bladder autoaugmentaion
                              排尿障礙治療中心 版權所有


Improved in bladder capacity but not Voiding
  pressure after autoaugmentation for IC
                           排尿障礙治療中心 版權所有



Conclusions
  Interstitial cystitis is more prevalent
   than previously realized
  A multiplicity of dynamic
   pathophysiological processes in bladder
  Vicious circle of increased urothelial
   permeability, inflammation, and nerve
   sensitization leads to chronicity of IC